Q&A With Jim Gnadt, BRAIN Initiative

June 27, 2019

The following Q&A is one in an occasional series of conversations with federal leaders in the behavioral and cognitive sciences.

Courtesy National Institutes of Health

Dr. Jim Gnadt, NINDS Program Director in Systems and Computational Neuroscience and Team Lead for the NIH BRAIN Integrative and Quantitative Approaches, has worked in systems, cognitive neuroscience, and neuroengineering for over 35 years.

Prior to taking the position at NINDS, Dr. Gnadt was an NIH-funded investigator since 1984, working on sleep physiology related to narcolepsy, quantitative neurophysiologic approaches in cognitive neuroscience, systems engineering to understand neural circuit dynamics, and neurological etiologies of eye behavior pathologies. He studied the neurological basis of cognitive, motor and sensory behavior by combining behavioral studies with in vivo and in vitro neurophysiology and systems control analyses.

Dr. Gnadt joined FABBS for our annual meeting in December 2018 and invited FABBS President Nora Newcombe and Board Member Jeff Zacks to his BRAIN Team this past February.

What can you tell us about progress of the first five years of the BRAIN Initiative? Any breakthroughs or discoveries to report?

We have published a mid-course summary in the Journal of Neuroscience (DOI:10.1523/JNEUROSCI.3174-17.2018) The State of the NIH BRAIN Initiative. To quote from that paper, “The promise of the BRAIN Initiative is to facilitate an understanding of how neural circuits produce behavior, thereby enabling us to understand the nature of circuit dysfunction in brain disorders.” Thus, the BRAIN Initiative focuses on understanding how the dynamic activities of the brain engender sensations, perceptions, systematic and plastic behaviors, thoughts and cognition, and mnemonics. To that end, the BRAIN Initiative has developed comprehensive brain cell atlases of several species, including invertebrates, rodents, fish, and primates (human and non-human). With the idea that developing powerful enabling technologies floats all boats, the BRAIN Initiative has developed an impressive toolkit of technologies for recording and manipulating the specific elements of the brain for experimental and therapeutic purposes. Further, the BRAIN Initiative is funding adventurous, multi-disciplinary projects and multiproject programs for understanding behaviors with the resolution of individual cell dynamics that make up the circuits and ensembles of the brain, in both non-human and human species. In addition, special programs have been created in training, in the science of data analyses and sharing, in computational and theoretical approaches, and in the neuroethics of investigative neural research on the organ that is the very essence of our introspective selves. Indeed, we have BRAIN Initiative investigators who are discovering how the brain generates very specialized human capabilities like language, speech and consciousness. For updated and specific accomplishments, news, and research opportunities, I would direct you to the NIH BRAIN Initiative website.

Please tell us a little bit about the role of Team E of the BRAIN Initiative.

Formally, our team is the Integrative and Quantitative Approaches Team. Sometimes, we are called the ‘circuits team,’ in that our emphasis is on understanding behavior in terms of dynamic circuit mechanisms. After all, even as our various neurological and psychiatric disorders may have origins in genetic anomalies, or traumatic or degenerative damage, the morbidity impacts are system failures of the circuits and functional areas of the brain. It is this question-driven, investigative component of the BRAIN Initiative that is slated to grow the most in the second half of the 12-year BRAIN Initiative.

Our members study behavior and cognition, can you tell us about any current or upcoming funding opportunities that would be most relevant to our disciplines?

One aspirational goal of the BRAIN Initiative is to understand how the brain thinks. Now, we don’t have a request for applications (RFA) specifically on behavioral, cognitive, or social neuroscience, but our portfolio of integrative, ‘circuit’ RFAs all require a well-defined behavior (or behavior of a welldefined neural system) that is investigated at the level of circuit mechanisms. After all, without exception, our various behaviors and thoughts, from unconscious homeostasis and automatic reflexes, to individual and social behaviors, to cognitive and mental capabilities, all derive from circuit activity. We have different funding mechanisms – large and small – to accommodate projects that are exploratory to comprehensive, single investigator labs to large research consortia, and within human and non-human neuroscience. We support research in behaviors as diverse as simple escape and decision behaviors, to psychophysics, to navigation, to consciousness, and social interactions. You can find the spectrum of grant mechanisms from our Team E on the NIH BRAIN website.

Any advice for our members interested in multidisciplinary brain research?

If you have an idea for investigation of any behavior or executive function in terms of the brain circuits involved, you should send a draft abstract to the contact Program Official in the RFA for a consultation. We can guide you to the most appropriate funding opportunity, even if it best fits another part of the BRAIN portfolio, or one of the NIH institutes that fund disorder-focused neuroscience research. If you are serious about pursuing multi-disciplinary research, our multi-PI R01s, human intracranial U01s, and team-science U01/U19 series is ideally suited for making collaborations among psychologists, biologists, physicians, engineers, physicists, and/or mathematicians. We especially encourage applications from early career investigators, and diverse expertise and backgrounds.

What are the next steps with the BRAIN Initiative?

There has been a year-long, mid-course evaluation of the BRAIN Initiative by an advisory committee to NIH Director Francis Collins and the Advisory Council of the Director. That ‘BRAIN 2.0’ committee will deliver a guiding document this month for the rest of the BRAIN Initiative until FY2026. For the most part, we are led to expect that it will encourage us to hold the course on most of what we have been doing for the last 5 years, with some modest strategic adjustments, along with encouragement to identify a signature accomplishment in improving human health. Looking forward, I hope we can continue the BRAIN Initiative efforts with an enduring enterprise in fundamental research neural science and health.